Thiazoles benzyl

Rearrangement to an open chain imine (165) provides an intermediate whose acidity toward lithiomethylthiazole (162) is rather pronounced. Proton abstraction by 162 gives the dilithio intermediate (166) and regenerates 2-methylthiazole for further reaction. During the final hydrolysis, 166 affords the dimer (167) that could be isolated by molecular distillation (433). A proof in favor of this mechanism is that when a large excess of butyllithium is added to (161) at -78°C and the solution is allowed to warm to room temperature, the deuterolysis affords only dideuterated thiazole (170), with no evidence of any dimeric product. Under these conditions almost complete dianion formation results (169), and the concentration of nonmetalated thiazole is nil. (Scheme 79). This dimerization bears some similitude with the formation of 2-methylthia-zolium anhydrobase dealt with in Chapter DC. Meyers could confirm the independence of the formation of the benzyl-type (172) and the aryl-type... 

Hthiated 4-substituted-2-methylthia2oles (171) at -78 C (Scheme 80). Crossover experiments at—78 and 25°C using thiazoles bearing different substituents (R = Me, Ph) proved that at low temperature the lithioderivatives (172 and 173) do not exchange H/Li and that the product ratios (175/176) observed are the result of independent metala-tion of the 2-methyl and the C-5 positions in a kinetically controlled process (444). At elevated temperatures the thermodynamic acidities prevail and the resonance stabilized benzyl-type anion (Scheme 81) becomes more abundant, so that in fine the kinetic lithio derivative is 173, whereas the thermodynamic derivative is 172. 

Cyclohexyl, benzyl, and phenethylthioamides give a low yield (4 to 10%) of the corresponding 2-substituted thiazoles (595, 649). 

Carbon disulfide readily reacts with a-aminonitriles giving 2-mercapto-5-aminothiazoles (213), (271, 293) which can be converted to 5-aminothiazoles unsubstituted in the 2-position (Scheme 110 and Table II-34a). If this reaction is carried out in the presence of benzyl chloride in phosphorus tribromide, a 2-S-substituted thiazole derivative (214) is obtained in quantitative yield (Scheme 111), with R = hydrogen or phenyl (68, 304). 

The catalyst, 3-benzyl-5-(2-hydroxyethyl )-4-methyl-l, 3-thiazoHum chloride, is supplied by Fluka AG, Buchs, Switzerland, and by Tridom Chemical, Inc., Hauppauge, New York. The thiazolium salt may also be prepared as described below by benzylation of 5-(2-hydroxyethyl)-4-methyl-l,3-thiazole which is commercially available from E. Merck, Darmstadt, West Germany, and Columbia Organic Chemicals Co., Inc., Columbia, SC. The acetonitrile used by the checkers was dried over Linde 3A molecular sieves and distilled under nitrogen, bp 77-78°C. The same yield of thiazolium salt was obtained by the checkers when benzyl chloride and acetonitrile from commercial sources were used without purification. 

A 250-mL, three-necked, round-bottomed flask is equipped with a mechanical stirrer, a reflux condenser fitted with a drying tube, and a stopper. The flask is charged with 14.3 g (0.1 mol) of 5-(2-hydroxyethyl)-4-methyl-1,3-thiazole, 12.7 g (0.1 mol) of freshly distilled benzyl chloride, and 50 mL of dry acetonitrile. The mixture is heated at reflux for 24 hr and cooled to room temperature. Crystallization is induced by scratching or... 

This procedure is representative of a new general method for the preparation of noncyclic acyloins by thiazol ium-catalyzed dimerization of aldehydes in the presence of weak bases (Table I). The advantages of this method over the classical reductive coupling of esters or the modern variation in which the intermediate enediolate is trapped by silylation, are the simplicity of the procedure, the inexpensive materials used, and the purity of the products obtained. For volatile aldehydes such as acetaldehyde and propionaldehyde the reaction Is conducted without solvent in a small, heated autoclave. With the exception of furoin the preparation of benzoins from aromatic aldehydes is best carried out with a different thiazolium catalyst bearing an N-methyl or N-ethyl substituent, instead of the N-benzyl group. Benzoins have usually been prepared by cyanide-catalyzed condensation of aromatic and heterocyclic aldehydes.Unsymnetrical acyloins may be obtained by thiazol1um-catalyzed cross-condensation of two different aldehydes. -1 The thiazolium ion-catalyzed cyclization of 1,5-dialdehydes to cyclic acyloins has been reported. 

Prior to the 1947 report by Cook and Heilbron on their novel synthesis, 5-aminothiazoles were mostly unknown in the literature. Previous syntheses included the Curtius degradation of ethyl thiazole-5-carboxylates which did not have general applicability there was also difficultly in obtaining the necessary starting materials. During a study on penicillin, Cook and Heilbron found that the reaction between methyl dithiophenylacetate and ethyl aminocyanoacetate gave what was initially believed to be ethyl phenylthionacetamidocyanoacetate 4. However further studies proved the compound to be 5-amino-4-carbethoxy-2-benzyl-thiazole 5, which was basic. 

Hetero-benzylic anionic reagents, derived from 2-alkyl-l,3-oxazoles, -1,3-thiazoles and -imidazoles and related compounds, are not covered in this section because these resemble metallo 1-azaenolates in their reactivity (Section D.l.3.5.). 

Fig. 17 Rapid preparation of imidazoles and thiazoles on solid-phase. Reagents a RNH2, (CH30CH2)2, MW 220°C, 15min, closed vessel b TFA in CH2CI2, rt, 60min. R = aliphatic, benzyl, or arylamines or arylhydrazine...

J ,3J ,4J ,5J )-2,5-bis(benzyloxy)-3,4-dihydroxy-Nd -bis (lS)-2-methyl-l-[(methylamino)carbonyl]propyl hexanediamide is a C2-symmetric HIV-1 protease inhibitor [29]. Derivatization in the para positions of the benzyl-oxy groups via microwave-assisted Stille reaction on the corresponding di-brominated inhibitor smoothly yielded the desired heteroarylated derivatives (Scheme 10). Interestingly, the 1,3-thiazole derivative showed a higher antiviral activity on the wild type virus than the lead compound. The activity remained at the same level in the presence of seriun. Unfortimately, a low activity was observed on mutants. 

Trlmethylsilyl)thiazole Thiazole, 2-(trimethylsilyl)- (10) (79265-30-8) J-0-Benzyl-3,4-isopropylidene-D-erythrose 1,3-Dioxolane-4-acetaldehyde,... 

A. Dondoni and P. Merino 21 DIASTEREOSELECTIVE HOMOLOGATION OF D-(R)-GLYCERALDEHYDE ACETONIDE USING 2-(TRIMETHYLSILYL)-THIAZOLE 2-O-BENZYL-3,4-ISOPROPYLIDENE-D-ERYTHROSE... 

A thiazolium amino acid (Taz) has been developed which can be utilized to mimic TDP-dependent enzyme function [52]. In this strategy, illustrated in Fig. 15, the commercially available amino acid 4-thiazolylalanine is incorporated into peptides by solid phase peptide synthesis. Prior to deprotection of the amino acid side chains and cleavage of the peptide from the resin, the thiazole amino acid is alkylated with an alkyl halide to generate the corresponding thiazolium amino acid having various N3-substituents (BzTaz = 3-benzyl-Taz, NBTaz = 3-nitrobenzyl-Taz). 

In some instances, sterically encumbered 2,5-dihydro-l,3,4-thiadiazoles do not eliminate nitrogen. Instead, cycloreversion leading to the starting materials or a new pair of diazo- and thiocarbonyl compounds was reported. Thus, a crystalline product of type 20, obtained from di(ferf-butyl)diazomethane and 2-benzyl-4,4-dimethyl-l,3-thiazole-5(477)-thione, was found to dissociate in solution to give the starting materials (42). In the case of (ferf-butyl)(trimethylsilyl)thioketone and... 

The best evidence for the photolytic decomposition of mercaptans and disulfides into free radicals involves photoinitiation of polymerization of olefins. Thus, photolysis of disulfides initiates the copolymerization of butadiene and styrene,154 as well as the polymerization of styrene207 and of acrylonitrile.19 Thiophenol and other thiols promote polymerization upon ultraviolet irradiation.19 Furthermore, the exchange of RS-groups between disulfides and thiols is greatly accelerated by light. Representative examples are benzothiazolyl disulfide and 2-mercapto-thiazole,90 tolyl disulfide and p-thiocresol, and benzyl disulfide and benzylmercaptan.91 The reaction probably has a free radical mechanism. Similar exchange reactions have been observed of RS-groups of pairs of disulfides have been observed.19... 

A. Dondoni and P. Merino, Diastereoselective homologation of D-(ft)-glyceraldehyde acetonide using 2-(trimethylsilyl)thiazole 2-0-benzyl-3,4,-0-isopropylidene-D-erythrose, Org. Synth. 72 21 (1993) The procedure has been checked by A. I. Meyers and G. P. Brengel, Colorado State University, USA. 

Propanoic Acide 2-Benzoylamino-2-(4-methoxy-benzyl)-3,3.3-tri-fluoro- E10b2, 180 (subst. 5-Oxo — 4.5-112 1,3-thiazole/HCl)... 

The nucleophilic nature of these radicals allows addition to carbon-nitrogen multiple bonds, and in selected cases this has been demonstrated. Suitable substrates for such additions include protonated pyridines, thiazoles and imidazoles (equation 183), and nitroalkyl anions359. Yamamoto and coworkers have also described cobalt-mediated multiple additions of carbon tetrahalides, benzyl bromides or a-bromo ketones to isocyanides, which are postulated to occur through the corresponding alkylcobalt(III) complexes360. 

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